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Meta-Analysis
. 2012 Aug 7:345:e4944.
doi: 10.1136/bmj.e4944.

Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis

S Mantha  1 , R Karp, V Raghavan, N Terrin, K A Bauer, J I Zwicker
Affiliations
Meta-Analysis

Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis

S Mantha et al. BMJ. .

Abstract

Objectives: To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection).

Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data sources: Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews.

Study selection: Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group.

Data extraction: Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators.

Results: Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53).

Conclusions: Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from US National Institute of Health for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow diagram of studies included in meta-analysis
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Fig 2 Adjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, all subgroups combined
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Fig 3 Unadjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, all subgroups combined
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Fig 4 Adjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, injectable formulation only
See this image and copyright information in PMC

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